Genetic Tests and Genetic Counseling How to Analyze Your Own Genome

Transcription

1 Genetic Tests and Genetic Counseling How to Analyze Your Own Genome

2 Genetic Tests for Huntington Disease Hun7ngton Disease Incurable brain disorder that runs in families Movement, cogni7ve, and psychiatric disorders Disease onset around age 40 Dominant muta7on in a gene on chromosome 4 Normal chromosomes 35 repeats of CAG Hun7ngton disease muta7on carriers more than 35 repeats If you have an affected parent, you have 50% chance of inheri7ng the disease muta7on Gene7c tests available If you know Hun7ngton disease runs in your family, would you be interested in taking the gene7c test? What if you haven t been tested but your children or parents want to get tested?

3 Genetic Test for Trisomy 18 Trisomy 18 a gene7c disorder in which a person has a third copy of material from chromosome 18 The extra gene7c material affects normal development Small head/jaws, low set ears, low birth weight, mental delay, muscle weakness Half of infants with this condi7on do not survive beyond the first week of life. Some children have survived to the teenage years, but with serious medical and developmental problems. Gene7c tests are available during pregnancy Would you like to get tested during the pregnancy?

4 Genetic Test for Tay-Sachs Disease Tay- Sachs disease a deadly disease of the nervous system passed down through families the body lacks hexosaminidase A, a protein that helps break down a chemical found in nerve 7ssue called gangliosides. Without this protein, gangliosides build up in cells, especially nerve cells in the brain. Symptoms usually appear when the child is 3 to 6 months old. The disease tends to get worse very quickly, and the child usually dies by age 4 or 5. Recessive: When both parents carry the defec7ve Tay- Sachs gene, a child has a 25% chance of developing the disease most common among the Ashkenazi Jewish popula7on About 1 in every 27 members of the Ashkenazi Jewish popula7on carries the Tay- Sachs gene Would you like to get tested for Tay- Sachs disease? Would the test results influence your decision on who to marry?

5 Genetic Tests for PKU Phenylketonuria (PKU) A rare condi7on in which a baby is born without the ability to properly break down an amino acid called phenylalanine Happens about 1 in 20,000 infants Causes profound neurological and cogni7ve damage Dietary interven7on (limi7ng intake of phenylalanine) can make a major difference in the child s health propsect Gene7c screening assay is a standard item for newborn screening panels

6 Growth of Genetic Testing Hudson et al., Nature Biotechnology, 2005

7 Genetic Tests Gene7c tests are ogen used for Diagnosis for prenatal, pediatric, and adult onset diseases Diseases that run in families for unaffected but concerned individuals Already being used widely for prenatal diagnosis Noninvasive or minimally invasive screening rou7nely done on pregnant women Maternal blood screening» Down syndrome: measures protein levels (PPAP- A and beta- HCG) in mother s blood Invasive tests done in response to risk factors, symptoms

8 Possible Benefits from Genetic Tests Clinical Avoidance of onset of disease Cura7ve treatment due to 7mely and accurate diagnosis Avoidance of harms from inappropriate treatment or monitoring Symptoma7c treatment Psychological or social Relief from uncertainty Personal planning Improved well- being Fulfilment of pa7ent wishes to be tested Public health Decrease popula7on morbidity and/or mortality from gene7c disease Decrease popula7on frequency of treatment- related morbidity or mortality

9 Genetics and Medicine Medical gene7cists MD training with subspecialty in medical gene7cs Ogen specialty training in pediatrics or internal medicine With whole- genome sequencing, the process for diagnosis is increasingly more complicated Gene- gene interac7on Gene- environment interac7on Gene7c counselors Trained in Master s program and board- cer7fied Works with medical gene7cists to offer counseling to pa7ents

10 Genetic Counseling Gene7c counseling explains the nature, usefulness and risks associated with gene7c tests assures that par7cipa7on in gene7c tes7ng is autonomous, or based on par7cipants understanding of the relevant informa7on Gene7c counselors iden7fy families at risk of gene7c condi7ons inves7gate the gene7c condi7on that is present in the family interpret informa7on about the disorder analyze inheritance paierns and risks of recurrence with the family, review the op7ons that are available Pre- and post- test counseling

11 Biochemical Assays vs. Genetic Tests Gene7c tests directly genotype individuals DNA Even if we determine the genotypes of individuals, we ogen cannot determine the effects of the muta7ons on phenotypes Biochemical Assays Assay for biochemical product of the pathway in which disease genes are ac7ve When there are different muta7ons that influence the same biochemical pathway, a single assay for the pathway can determine a func7onal deficit

12 Biochemical Assays vs. Genetic Tests Why not biochemical assays? Advantages of gene7c tests Possible to detect the poten7al func7onal deficit before the symptoms (imbalance in the biochemical pathways) occur Early interven7on to reduce the damage from the disease Can be cri7cal for newborns Non- invasive Can be performed on cell sample from blood or from swabbing the inside of the cheek Do not need the genes to be expressed biochemical assays may involve invasive, difficult, and expensive procedure

13 Karyotyping Karyotyping Taking dividing cells from the fetal sample and break them open on glass slides so that individual mito7c chromosomes spread out in a loose field The slides are stained and photographed Used for autosomal trisomies and sex chromosome anomalies Turner (XO) syndrome Klinefelter (XXY) syndrome

14 Practical Challenges Interpre7ng the gene7c tests result can be challenging for complex diseases Individual pa7ents may rely on false informa7on on the web! Reliable online resources such as GeneClinics, OMIM (Online Medelian Inheritance in Man) are becoming available Consult medical gene7cists or gene7c counselors Informa7on on rare gene7c disorders may be hard to find even at a clinic Developing cost- effec7ve gene7c tests Development of gene7c tests follows discovery of disease genes Less incen7ves to develop gene7c test for rare diseases For newly discovered genes, gene7c test may not be available Pa7ents can par7cipate in research- based gene7c tes7ng

15 Genetic Tests for Complex Traits With whole- genome sequencing, in the future, gene7c tests for complex traits will be available Challenges in interpre7ng test results for complex traits Effect size of each muta7on may be very small The posi7ve test results do not necessarily mean 100% certainty in developing the par7cular phenotype Developing phenotypes only under certain condi7ons that are difficult but not impossible to avoid How to interpret the maybe results? Gene7c screening for non- disease phenotypes such as cosme7c traits, IQs

16 Genetic Tests for Breast Cancer BRCA1 and BRCA2 tes7ng 36-85% chance of developing breast cancer for BRCA- posi7ve women 13% chance for the general popula7on Possible risk- reducing strategies for BRCA- posi7ve women Increased surveillance for early detec7on Risk- reduc7on surgery to remove part of breast and ovarian 7ssues Changing life style But the test results are not defini7ve answers to whether you ll develop breast cancer!

17 Other Types of Genetic Tests Pharmacogenomic tes7ng Pa7ents requiring specific medicines might undergo a gene7c test to determine the likely rate of drug metabolism, thus providing the doctor with cri7cal informa7on for proper dosage E.g., Cytochrome P450 (CYP450) tests Our body contains many P450 enzymes to process drug Gene7c varia7on in these enzymes can affect how each person responds to the drug Iden7fica7on of individuals Paternity test, iden7fying rela7ves Law enforcement iden7fying criminals

18 Summary Gene7c tests have been used mainly for prenatal screening but will be more widely used for adult- onset diseases in the future Gene7c counselor and medical gene7cists can assist pa7ents for interpre7ng the results from gene7c tests Issues involved in interpre7ng the test results Ethical issues what ac7ons to take given the test results Challenges in interpre7ng results for complex traits